Alexander A. Bialasiewicz

Optical coherence tomography in uveitis patients

PURPOSE To evaluate optical coherence tomography in allergy-prone uveitis patients. METHODS Thirty-four patients (43 eyes) with posterior uveitis (31 eyes) and intermediate uveitis (12 eyes) were evaluated by fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Follow-up examinations used optical coherence tomography in allergy-prone patients. RESULTS Optical coherence tomography identified epiretinal membranes, which were removed surgically (three eyes); persistent cystoid macular edema, which resolved with cytotoxic treatment (12 eyes); and juxtafoveolar membranes, which were treated by diode laser (six eyes) and excision (two eyes). CONCLUSION Optical coherence tomography may provide useful information on complications developing in uveitis patients.

Immunsuppressive Therapie mit Mycophenolat Mofetil (CellCept®) in der Behandlung der Uveitis

ZusammenfassungFragestellung. Ziel der vorliegenden multizentrischen Studie war, die Wirksamkeit von Mycophenolat Mofetil (MMF) als Monotherapeutikum bei verschiedenen Formen der Uveitis zu untersuchen. Patienten und Methode. Zehn Patienten mit anteriorer Uveitis (n=3), intermediärer Uveitis (n=2), Panuveitis (n=4) und retinaler Vaskulitis (n=1) wurden in einer prospektiven Studie mit 2×1 g MMF/Tag therapiert. Ergebnisse. Der Behandlungszeitraum betrug 1–12 Monate. Bei 8 Patienten zeigte sich unter der MMF-Therapie kein weiteres Rezidiv. Zwei Patientinnen wurden erst durch Umstellung auf Methotrexat bzw. durch eine begleitende Steroidmedikation rezidivfrei. An Nebenwirkungen klagte ein Patient über Diarrhö, die zum Absetzen der Therapie führte. Bei einer Patientin kam es 10 Monate nach Therapiebeginn zu Übelkeit, Erbrechen und Haarausfall. Schlussfolgerung. Die Immunsuppression mit MMF hat bei 8 von 10 Uveitispatienten zu einer Beruhigung der Entzündungsaktivität geführt. Die Nebenwirkungen sind eher milde verglichen mit denen anderer Immunsuppressiva.AbstractBackground. Severe forms of uveitis can often only be managed sufficiently with systemic immunosuppression. All available drugs are known for their relative high rate of side-effects. Mycophenolate mofetil (MMF), an immunosuppressant successfully used in management after organ transplantation and many autoimmune diseases, has shown remarkably less side-effects when used for various forms of uveitis in monotherapy or in combination with corticosteroids. The aim of this multicenter-study was to investigate if monotherapy with MMF is effective in various forms of uveitis. Method and patients. Ten patients with anterior uveitis (n=3), intermediate uveitis (n=2), panuveitis (n=4) and retinal vasculitis (n=1) were treated in a prospective study with 2×1 g MMF daily. Previous immunosuppression had been discontinued because of side-effects or ineffectivity in all patients. In these patients MMF was given in addition to the other immunosuppressant at the beginning of treatment. Results. The follow-up time ranged from 1 to 12 months (mean 4.5 months). Under therapy with MMF (monotherapy in 4 patients, additional prednisolone in 5 patients and additional metotrexate in 1 patient) 8 patients remained free of recurrences. In one female patient depression of inflammation activity was only achieved after cessation of therapy with Cyclosporin A in combination with MMF and a switch to methotrexate. Another patient with a bilateral uveitis was free of recurrences in only one eye, the second eye did not develop recurrence due to the additional corticosteroid treatment. Side-effects were diarrhoea in one patient and probably gastrointestinal problems in another (leading to cessation of therapy in both patients) and in another case nausea, vomitus and alopecia 10 months after beginning therapy. Conclusions. MMF as a new immunosuppressant stopped inflammation or drastically reduced the rate of recurrences in 8 out of 10 patients with uveitis which was previously not brought under control by other immunosuppressants. The side-effects were tolerable in comparison with other immunosuppressive agents. More patients, longer follow-up times and a comparative study with Cyclosporin A are required to assess the long-term therapeutical success.

α/β− and γ/δ TCR+ lymphocyte infiltration in necrotising choroidal melanomas

AIM To detect specific tumour infiltrating T cells (TIL) carrying antigen specific MHC-I restricted receptor genes on necrotising and non-necrotising malignant melanomas and to correlate the findings with clinical data. METHODS α/β− and γ/δ− TIL were determined by immunohistochemical staining in melanomas of patients with known follow up of more than 10 years. An antigen retrieval method was used to determine variable genes δ1 and γ1 on TCR+ cells by an anti-TCR Vδ1 and anti-CrγM1, and of Vα and Vβ TCR+ by an anti-pan-TCR+α/β antibody. RESULTS Intratumoral TIL were present in 86 of 113 (76.1%) necrotising melanomas (NMM)v 21 of 100 (21%) in non-necrotising melanomas (MM); of these, Vα/β− TCR+ cells were present in 52 of 74 (70.3%) TIL harbouring NMMv four of 21 (19%) MM; Vγ1 in 29 of 74 (39.2%) NMM v two of 21 (10%) MM; and Vδ1 in 39 of 74 (52.7%) NMM v three of 21 (14%) MM. Extratumoral lymphocytic infiltration was seen in 86 (76.1%) NMM including Vα/β TCR+ cells in 10 (11.6%) cases, v five (5%) MM cases with no Vα/β TCR+ cells detected. Vγ1 and Vδ1 TCR+ cells were not found in extratumoral infiltrates. CONCLUSIONS In NMM, the median survival was 69.3 (range 6–237) months, 19 of 74 patients (25.7%) survived 5 years, and mortality was associated with advanced stage (p<0.001), patient age (p<0.023), and extent of necrosis (p<0.048). Survival was increased with evidence of Vγ1 and Vδ1 TCR+ cells (p<0.026).

Endophthalmitis nach Kataraktoperation Disponierende Faktoren, Erreger und Therapie

ZusammenfassungHintergrund: Die infektiös bedingte exogene Endophthalmitis stellt eine ernste Komplikation nach Kataraktoperation dar. Sie ist trotz moderner medikamentöser und chirurgischer Behandlungsmethoden oftmals schwer therapierbar. Patienten und Methoden: In einer retrospektiven Studie wurden alle Patienten (n=36) untersucht, die zwischen Januar 1989 und Dezember 1997 an der Universitäts-Augenklinik Hamburg-Eppendorf (UKE) aufgrund einer Endophthalmitis nach Kataraktextraktion behandelt worden waren. Ergebnisse: Von 36 Patienten wurden der Klinik 29 (80,6%) von außerhalb zugewiesen. 14 Patienten (38,9%) hatten eine Endophthalmitis nach ambulanter Kataraktextraktion entwickelt. 7 Patienten (19,4%) waren stationär in der Augenklinik UKE operiert worden. Bei 29 der Patienten (80,6%) wurde eine Vitrektomie vorgenommen. Ein Erreger konnte aus 50% der Vorderkammer- bzw. Glaskörperproben isoliert werden, am häufigsten Koagulase-negative Staphylokokken (n=4). Zu den prädisponierenden Faktoren der Endophthalmitis zählten Diabetes mellitus (27,8%), perioperativer Glaskörperverlust (19,4%), systemische Kortikosteroidtherapie (13,9%) und Wunddehiszenz (11,1%). Von 27 nachuntersuchten Patienten (75%) erreichten 16 (59,3%) einen Visus von 0,05 oder besser (durchschnittlicher Visus 0,5). Bei 4 Patienten (13,8%) mußte eine Enukleation vorgenommen werden. Schlussfolgerung: In der vorliegenden Studie konnte bei etwa 60% der Patienten mit einer postoperativen Endophthalmitis das Auge erhalten und eine optische Rehabilitation durch chirurgische Intervention erzielt werden.SummaryBackground: Infectious exogenous endophthalmitis is a serious complication after cataract surgery. Despite modern pharmacological and surgical methods, its treatment is still difficult. Patients and methods: In a retrospective study the records of all patients treated for endophthalmitis following cataract extraction at the Department of Ophthalmology of the University Hospital in Hamburg between January 1989 and December 1997 were assessed. Results: Of 36 patients treated for endophthalmitis, 29 (80.6%) had been referred. In 14 (38.9%) of these 29 patients endophthalmitis had occurred after outpatient cataract surgery. Seven patients (19.4%) had been treated as inpatients at the University Eye Hospital Eppendorf. Vitrectomy was performed in 80.6% of the cases. An infectious agent was isolated from 50% of diagnostic probes. The most common organism isolated were coagulase-negative staphylococci (4 cases). Predisposing factors for the development of endophthalmitis were diabetes (27.8%), intraoperative loss of vitreous (19.4%), application of systemic steroids (13.9%) and wound dehiscence (11.1%). Of 27 patients (75%) followed up, 16 (59.3%) had a final visual acuity of 20/400 or better (mean 20/40). An enucleation had to be performed in 4 patients (13.8%). Conclusion: In this study, approximately 60% of patients with endophthalmitis following cataract extraction had their globes preserved and a good visual outcome after appropriate surgical interventions.

Coxsackievirus B3-associated panuveitis.

A 29-year-old woman suffered from headaches, diarrhoea, and high grade fever followed by a unilateral retinal vasculitis, papillitis, and chorioretinitis. Abnormal electrocardiographic findings and antibody titre dynamics strongly suggested a coxsackievirus B3 infection. With respect to prior observations on coxsackievirus B group associated uveitis this viral infection may be considered in patients with well defined extraocular manifestations and uveitis.

Korrelation von 55 Kontaktlinsenflüssigkeiten mit Direktabstrichen von der Augenoberfläche bei symptomatischen Kontaktlinsenträgern

ZusammenfassungHintergrund. Es wurde der Frage nachgegangen, ob die mikrobiologische Untersuchung der Aufbewahrungsflüssigkeit von Kontaktlinsen zu einem Nachweis der Erreger für Keratitiden und Umweltkontaminanten führt. Patienten und Methoden. In einer prospektiven nicht randomisierten Kohortenstudie wurden 55 Träger weicher Kontaktlinsen mit Keratitis mit Direktabstrich/-abradat von Kornea und Konjunktiva untersucht und die Kontaktlinsenflüssigkeiten der Aufbewahrungsbehälter mikrobiologisch aufgearbeitet. Ergebnisse. In den gebrauchten Kontaktlinsenflüssigkeiten wurden 55 Erreger in 42 der Behälter gefunden. Eine signifikante Korrelation mit den Direktabstrichen von der Bindehaut/Hornhaut ergab sich für Pseudomonas, Enterobacter, Serratia, S. aureus, Streptococcus faecalis und Akanthamöben, nicht dagegen für Bacillus, Alcaligenes und koagulasenegative Staphylokokken. Pilze wurden in keinem Falle isoliert. Je ausgeprägter der klinische Befund war, desto häufiger wurden gramnegative Bakterien isoliert. Schlussfolgerungen. Die mikrobiologische Analyse der Kontaktlinsenaufbewahrungsflüssigkeiten bestätigt, dass die verantwortlichen Erreger ausnahmslos in der Flüssigkeit zu finden sind. Eine relevante Zusatzinformation aus Hornhautabradaten kann nur für Akanthamöben abgeleitet werden.AbstractBackground. The microbiological examination of contact lens storage solutions may reveal the etiological organisms resposible for keratitis and additionally harbour environmental contaminants. Patients and methods. From 1995 to 1998, conjunctival and corneal smears and scrapes, as well as the storage solutions of 55 soft contact lens wearers were examined microbiologically in a prospective non-randomised cohort study involving 53× unilateral and 2× bilateral cases of keratitis. Results. In 42 of the in-use contact lens storage solutions, the following organisms were found: 8×Bacillus sp., 7×P. aeruginosa and 8× other pseudomonads, 6×Alcaligenes xylosans, 4×Serratia liquefaciens, 4×Enterobacter sp., 4× coagulase negative staphylococci, 3×Serratia marcescens, 3×S. aureus, 2×Streptococcus faecalis, 1×Klebsiella oxytoca and 5×Acanthameba. A significant correlation of ocular cultures was found for Pseudomonas, Enterobacter, Serratia, S. aureus, S. faecalis and Acanthameba, but not for Bacillus, Alcaligenes, and coagulase negative staphylococci. Fungi were not found. The more pronounced the clinical picture, the more Gram-negative bacteria were isolated. Conclusions. The microbiological examination of soft contact lens storage solutions of 55 keratitis patients confirmed that the microbes responsible were to be found in the fluid, in addition to environmental contaminants.

Detection of HPV-20, HPV-23, and HPV-DL332 in a solitary eyelid syringoma

PURPOSE To report evidence of many human papillomavirus types occurring in a solitary syringoma clinically appearing as a papilloma. METHODS A 57-year-old man presented with a 10-year history of an upper eyelid tumor. Histopathology, human papillomavirus-nested polymerase chain reaction, human papillomavirus-DNA cloning into vector pCR2.1, sequencing, and computer-assisted evaluation were performed. RESULTS Histopathology demonstrated a solitary benign syringoma. HPV-20 and HPV-23 were present in one clone each, and HPV-5-related HPV-DL332 was present in 9 clones. CONCLUSION Many human papillomavirus types may be detected in an ocular syringoma.

Tapioca melanomas of the iris: immunohistology and report on two cases.

Abstract · Background: Tapioca-like tumors are rare, and their benign or malignant nature is obscure without histological work-up. We report on the clinical and histological features of different types of tumors in two patients. · Case report: Two patients aged 17 and 45 years presented with brownish iris masses increasing in size. Full-thickness en bloc excision of melanocytic tumors (5.5 mm and 7.0 mm in diameter) was carried out. Histological work-up revealed a nevus cell nevus in the young patient and an epithelioid malignant melanoma in the middle-aged patient evolving from the ciliary body. Staining for HMB-45 was marked in both tumors, for S-100 low in the nevus and marked in the melanoma, and for p53 negative in the nevus and positive in the melanoma. Ki67 stains were negative. · Conclusion: We propose that excision of anteriorly located pigmented tumors that increase in size is indicated in order to deter-mine whether they are benign or malignant. In these case reports, tapioca-like tumors include a benign and a malignant entity. To our knowledge, a nevus cell nevus presenting as a tapioca-like tumor has not previously been described. Curative surgery and histological and immunohistological evaluation are required to characterize the malignant potential of these tumors and the prognosis.

Combined immunosuppressive and surgical therapy of necrotic keratitis in rheumatoid arthritis

SummaryIntroduction: Areactive forms of keratitis in patients with seropositive rheumatoid arthritis are inflammations threatening the visual acuity and integrity of the eye. They commonly occur in a rheumatologically inactive interval and have a poor prognosis. A retrospective evaluation of medicamentous and surgical strategies for a curative therapy with optical rehabilitation is necessary to optimise the treatment of patients with necrotic sclerokeratitis. Patients and methods: A total of 27 eyes of 22 patients (14 women and 8 men, ranging in age at the time of operation from 40 to 88 years; mean 68.7 years) with seropositive rheumatoid arthritis and secondary Sjögrens syndrome were reviewed retrospectively. There were 17 eyes with necrotic keratitis and 9 eyes with necrotic sclerokeratitis. In one eye, necrotic sclerokeratitis with bacterial transmigrating keratitis and hypopyon occurred. Operations: In 8 cases we performed a perforating mini-keratoplasty, in 16 cases a tectonic and optical perforating keratoplasty, in 3 cases a tectonic sclerokeratoplasty, in 9 patients a combined keratoplasty and cataract extraction with posterior chamber lens implantation and in 1 case a partial conjunctival plasty. Follow-up ranged from 7 months to 4 years (average 2.8 years). Results: In all eyes, a sufficient tectonic and primary curative effect was achieved only under cyclophosphamide immunosuppression. In 3 cases, a rekeratoplasty had to be performed because of recurrent keratitis after changing the systemic cyclophosphamide therapy to methotrexate, glucocorticosteroids or non-steroid antiphlogistic agents. Visual acuity outcome was depending on the eccentricity of the keratoplasty and earlier affections of the eye. Postoperatively, the visual acuity improved in 23 eyes. In 3 cases, no change of visual acuity was achieved. Visual acuity deteriorated in one case from counting fingers to hand motions. Peri- and postoperative complications during the follow-up period were corneal infiltration around sutures in 4 eyes, graft rejecting reactions in 3 cases, and sicca syndrome in 6 cases. Conclusions: The intensive cooperation of ophthalmologists and rheumatologists enables the successful treatment of apparently hopeless situations in necrotic sclerokeratitis in patients with seropositive rheumatoid arthritis. The rate of complications under an immunosuppressive therapy with cyclophosphamide was found at average 2.8 years follow-up to be low. The indication for the combined therapy depends on the ophthalmological findings; rheumatologists and ophthalmologists should decide on the appropriate dosage for the systemic cyclophosphamide therapy. Topical glucocorticosteroid therapy alone is contra-indicated.ZusammenfassungHintergrund: Areaktive Keratitiden bei chronischer Polyarthritis (cP) sind den Visus und die Integrität des Auges bedrohende Entzündungen, die meist in einem rheumatologisch inaktiven Intervall auftreten und eine schlechte Prognose haben. Die retrospektive Auswertung medikamentöser und chirurgischer Strategien zur kurativen Therapie mit optischer Rehabilitation ist für die Optimierung der Behandlung dieser Patienten wichtig. Patienten und Methoden: Untersucht wurden 22 Patienten mit 27 erkrankten Augen bei bekannter seropositiver chronischer Polyarthritis und sekundärem Sjögren-Syndrom. 14 Patienten waren weiblich, 8 männlich. Das Patientenalter betrug zum Zeitpunkt der Operation 40–88 Jahre (Mittelwert: 68,7 Jahre). 17 Augen hatten eine nekrotisierende Keratitis, 9 Augen eine nekrotisierende Sklerokeratitis und ein Auge eine Sklerokeratitis mit bakterieller Durchwanderungskeratitis und Hypopyon. Es wurden eine tektonische und optische perforierende Keratoplastik in 16 Fällen, eine tektonische Mini-Keratoplastik in 8 Fällen und eine tektonische Sklerokeratoplastik in 3 Fällen durchgeführt. Kombinierte Eingriffe mit simultaner Hinterkammerlinsenimplantation erfolgten davon 9 mal, mit partieller Bindehautdeckung einmal. Der Nachbeobachtungszeitraum lag zwischen 7 Monaten und 4 Jahren, im Durchschnitt bei 2,8 Jahren. Ergebnisse: Ein tektonischer und primär kurativer Effekt wurde bei allen Augen nur unter Immunsuppression mit Cyclophosphamid erzielt, in 3 Fällen mußte nach Umstellung der systemischen Therapie von Cyclophosphamid auf Methotrexat, Glukokortikoide oder nichtsteroidale Antiphlogistika bei rezidivierender Keratitis eine Re-Keratoplastik durchgeführt werden. Der Visusverlauf war abhängig von der Exzentrizität der Keratoplastik und von Vorerkrankungen. In 23 Fällen stieg der Visus postoperativ an. In 3 Fällen blieb der Visus unverändert, in einem Fall fiel er postoperativ von Fingerzählen auf Handbewegungen ab. An peri- und postoperativen Komplikationen traten im Nachbeobachtungszeitraum 4× Fadeninfiltrate, 3× Transplantatreaktionen und 6× eine Sicca-Problematik auf. Schlußfolgerungen: Durch eine intensive interdisziplinäre Kooperation von Ophthalmologen und Rheumatologen können aussichtslos erscheinende Situationen am Auge beherrschbar werden. Die Häufigkeit von Komplikationen unter Immunsuppression mit Cyclophosphamid ist zumindest mittelfristig im Nachbeobachtungszeitraum von durchschnittlich 2,8 Jahren als gering einzuschätzen. Die Indikation zur systemischen Therapie hängt vom augenärztlichen Befund ab, die Dosierung der systemischen Immunsuppression erfolgt durch Rheumatologen und Ophthalmologen. Eine alleinige topische Glukokortikoidtherapie ist kontraindiziert.

α/β- andγ/δ-T cell-receptor-positive lymphocytes in healthy and inflamed human conjunctiva

Abstract• Background: The possible existence and distribution patterns of α/β- and γ/δ-TCR+ cells, which are important constituents of immune surveillance and act via the CD3+ cell complex have not yet been elucidated in the healthy and inflamed conjunctiva. • Materials and methods: Paraffin-embedded conjunctival specimens included 18 from 18 patients with ocular cicatricial pemphigoid (OCP), 20 from 20 healthy controls, 6 from 6 patients with lye burns, and 6 from 2 patients with Stevens-Johnson syndrome; all were worked up by histology and immunohistochemistry. • Results: α/β-TCR+ cells were visualized in the conjunctival epithelium and stroma of healthy persons, OCP, lye burns and Stevens-Johnson syndrome. α/β-TCR+ cells and a small number of γ/δ-TCR+ cells were observed in the corneal epithelium and stroma of patients who have failing corneal grafts. After ileal mucosa transplantation to the epibulbar conjunctiva, membrane staining changes to nuclear and cytoplasmic staining. Treatment with systemic cytotoxic drugs abolishes all α/β-TCR+ and γ/δ-TCR+ cells. • Conclusions: α/β-TCRu+ cells can be found in the non-infected epithelium and stroma of the healthy and inflamed (OCP, lye burns, and Stevens-Johnson syndrome) conjunctiva, as well as in the corneal epithelium and stroma of failing corneal grafts, whereas γ/δ-TCR+ cells are absent. A small number of γ/δ-TCR+ cells are present in the corneal stroma and adjacent conjunctival epithelium of patients with chronic corneal graft rejection or after transplantation of gut tissue. Further investigations may establish the role, if any, of these T-cell subsets in immune surveillance of the non-infected outer eye and in corneal graft rejection.